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The unusual pathobiology of hemoglobin constant spring red blood cells
SL Schrier, A Bunyaratvej, A Khuhapinant, S Fucharoen, M Aljurf, LM Snyder, CR Keifer, L Ma and N Mohandas
Division of Hematology, Stanford University, CA, USA.
Hemoglobin Constant Spring (HbCS) is the most common nondeletional
alpha-thalassemic mutation and is an important cause of HbH-like disease in
Southeast Asia. HbCS variants have an almost normal mean cell volume (MCV)
and the anemia is more severe when compared with other alpha-thalassemic
variants. We explored the pathobiology of HbCS red blood cells (RBCs)
because the underlying cause(s) of this MCV "normalizing" effect of HbCS
and the more severe anemia are not fully explained. HbCS containing RBCs
are distinctly overhydrated relative to deletional alpha-thalassemia
variants, and the derangement of volume regulation and cell hydration
occurs early in erythroid maturation and is fully expressed at the
reticulocyte stage. Furthermore, the membrane rigidity and membrane
mechanical stability of HbCS containing RBCs is increased when compared
with HbH and alpha-thalassemia-1 trait RBCs. In seeking the cause(s)
underlying these cellular alterations we analyzed membranes from HbCS and
deletional alpha-thalassemic variants and found that in addition to
oxidized beta-globin chains, oxidized alpha cs- globin chains are also
associated with the membranes and their skeletons in HbCS containing RBCs.
We propose that the membrane pathology of HbCS variants is caused by
combination of the deleterious effects induced by membrane-bound oxidized
alpha cs- and beta-globin chains. The membrane alterations induced by alpha
cs chains are more akin to those induced by beta A-globin chains than those
induced by the alpha A-globin chains that accumulate in the
beta-thalassemias. Thus, each globin chain, alpha cs, alpha A, beta A,
appears to produce its own form of membrane perturbation.
Volume 89,
Issue 5,
pp. 1762-1769,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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